1. Field of the Invention
The systems and methods of this invention relate to electrical stimulation of the heart and other body tissues by means of an implantable device. Specifically the present invention relates to systems and methods for providing such stimulation without the use of conventional lead/electrode systems. More specifically, the present application provides systems and methods for treatment of heart failure and for terminating heart arrhythmias with implantable pacing systems and components.
Electrical stimulation of body tissues is used throughout medicine for treatment of both chronic and acute conditions. Among many examples, peripheral muscle stimulation is reported to accelerate healing of strains and tears, bone stimulation is likewise indicated to increase the rate of bone regrowth/repair in fractures, and nerve stimulation is used to alleviate chronic pain. A commonly implanted device utilizing electrical stimulation is the cardiac pacemaker. Further there is encouraging research in the use of electrical stimulation to treat a variety of nerve and brain conditions, such as essential tremor, Parkinson's disease, migraine headaches, functional deficits due to stroke, and epileptic seizures.
Devices to provide such stimulation may be applied externally in some cases, or in other cases it is more advantageous to implant all or part of the device. This invention pertains to devices in which at least one portion providing direct electrical stimulation to the body tissue is either permanently or temporarily implanted. Such devices include pacemakers, implantable defibrillators, and other devices for stimulating cardiac and other tissues.
Electrical energy sources connected to electrode/lead wire systems have typically been used to stimulate tissue within the body. The use of lead wires is associated with significant problems such as complications due to infection, lead failure, and electrode/lead dislodgement.
The requirement for leads in order to accomplish stimulation also limits the number of accessible locations in the body. The requirement for leads has also limited the ability to stimulate at multiple sites (multisite stimulation). For instance, the treatment of epilepsy could require a minimum of perhaps 5 or 6 stimulation sites. Other diseases, such as Parkinson's disease, would benefit from more stimulation sites than the two utilized in current systems.
Beyond the problems of outright failure and placement difficulties, pacemaker leads inherently cause problems for pacemaker systems by acting as antennae, coupling electromagnetic interference (EMI) into the pacemaker electronics. Particularly problematic is interference with cardiac electrogram sensing and signal processing circuitry. With the exponential rise in the number of cellular telephones, wireless computer networks, and the like, pacemaker lead induced EMI will continue to spur increased complexity in the design of, and require significant testing of pacemaker devices.
The most commonly implanted stimulation device is the cardiac pacemaker. A pacemaker is a battery-powered electronic device implanted under the skin, connected to the heart by an insulated metal lead wire with a tip electrode. Pacemakers were initially developed for and are most commonly used to treat bradycardia, slow heart rates, which may result from a number of conditions. More recently, advancements in pacemaker complexity, and associated sensing and pacing algorithms have allowed progress in using pacemakers for the treatment of other conditions, notably heart failure (HF) and fast heart rhythms (tachyarrhythmia/tachycardia).
In a common application, pacemaker leads are placed through the skin into a subclavian vein or branch to access the venous side of the cardiovascular system. Such systems can be either single chamber with a lead placed in either the right atrium or right ventricle, or dual chamber systems with one lead placed in contact with the right atrial wall and a second lead placed in contact with the right ventricular wall. For the treatment of HF, through what is commonly known as cardiac resynchronization therapy, bi-ventricular pacing is utilized, requiring that an additional lead be placed in contact with the left ventricle. To access the left ventricle, the third lead is typically advanced into the right atrium, into the orifice of the coronary sinus, and then maneuvered through the coronary sinus veins to a position on the epicardial aspect of the posterolateral or lateral wall of the left ventricle.
Though now less common after nearly five decades of improvement in designs and materials, failure of a pacemaker lead is still a significant risk to the patient—not only for the loss of pacing which may represent a life-threatening event, but also due to the fact that once implanted, pacemaker leads are only extracted with a procedure or surgery of significant risk. Additionally, the location of an existing non-functional lead, if not removable, may prevent implantation of a replacement lead. Pacemaker leads may fail due to a number of reasons including breakage of the insulator or conductor and loose or incompatible connectors.
In biventricular pacing for HF, placement of the third lead to contact the left ventricle remains a significant problem. The coronary sinus is a complicated venous pathway with multiple branches which bend and narrow with considerable variation as they extend distally onto the epicardium of the left ventricle. Placement of the third lead requires significant skill on the part of the physician. In order to provide adequate steerability and pushability, the design of the left ventricular lead or a lead introduction system/device is much more complicated than regular pacing leads. Often the positioning and placement of the left ventricular lead can take over an hour to perform, exposing the patient to increased fluoroscopy radiation and increased procedure risks. In some patients (7.5% in the MIRACLE study) an acceptable lead placement is not possible due to anatomic constraints or phrenic nerve pacing. Additionally, lead dislodgement and loss of pacing have been common complications in the use of these coronary sinus leads (10-20% complication rates within the first 6 months of device placement).
The requirement for a lead to accomplish left ventricular stimulation limits the placement to either the coronary sinus vein as described above or an epicardial placement which uses surgical techniques to place the lead on the epicardium and then tunneling of the lead to the location of the pacing device for connection. Left ventricular leads are not placed inside the heart chamber as they are for the right-sided leads for several reasons. They would have to be chronically situated retrograde across the aortic valve or transeptally across the mitral valve which could cause aortic or mitral valvular insufficiency. The patients would be subject to risk of thromboembolic complications from having leads in the arterial circulation. Retrograde insertion of a pacing lead into the left ventricle via the aorta would require a permanent arterial puncture for lead insertion, permanent aortic regurgitation, and permanent anticoagulation to prevent thrombus formation. Alternatively, atrial transeptal puncture from the right atrium to insert a pacing lead into the left atrium or left ventricle also requires permanent anticoagulation, and for left ventricular sites, would cause mitral regurgitation. Moreover, all pacemaker leads are associated with an incidence of infection, and the risk of valvular endocarditis is greater in the left heart.
In patients receiving a bi-ventricular pacing system, site selection for placement of the left ventricular lead has been found to be critically important in order to provide hemodynamic benefit. Up to 40% of patients receiving bi-ventricular pacing for the treatment of HF do not benefit (i.e. hemodynamic measures and HF functional class do not improve or deteriorate). The most important cause for lack of benefit is thought by experts to be due to suboptimal or incorrect left ventricular stimulation site. However, restrictions imposed by the difficulty of positioning and by the anatomy of the coronary sinus and its branches often limit the ability to select a more optimal left ventricular pacing site. The ability to precisely select the left ventricular site for stimulation in combination with right ventricular stimulation, would aid in the treatment of HF.
Moreover, left ventricular stimulation currently is restricted to sites on the epicardial (outer) surface of the heart; the coronary sinus courses on the epicardium, and surgically implanted left ventricular leads are screwed into the epicardium. Recent data indicates that endocardial (inside lining) or subendocardial (inside layer) stimulation sites in the left ventricle provide additional benefit.
Importantly, clinical trial data now suggest that pacing of the left ventricle alone may result in hemodynamic benefit equivalent to that of bi-ventricular pacing. Thus, a leadless pacing system has the potential to accomplish the benefit of bi-ventricular pacing without the need for a right ventricular pacing lead or electrodes.
It would also be beneficial to provide more physiological right ventricular pacing for patients without HF. In normal physiology, the right ventricle is first stimulated in the upper septal area, and then the impulse travels down specially conducting pathways to the right ventricular apex. However, pacing the right ventricle is virtually always accomplished from a lead tip electrode located in the right ventricular apex, such that the subsequent conduction pathway is abnormal and slow. Clinical trials have recently shown that in patients with and without A-V block, pacing from the right ventricular apex can result in increased total mortality and re-hospitalization for heart failure. Thus it would be advantageous to be able to pace the right ventricle at more physiological locations such as the upper septum. The most physiological location to pace the ventricle in patients with sinus nodal or A-V junction conduction disease is to directly pace the His bundle. However, this location is very difficult to access from the superior (vena cava) approach mandated by lead-based systems that attach to a pectorally implanted pulse generator. It would be beneficial to deliver electrodes from the inferior (vena cava) approach via the femoral veins, in which catheter positioning in the A-V junction region is known to be easier. For instance, in a published series of permanent His bundle pacing, the His bundle was first identified using a temporary catheter inserted via the femoral vein, and this catheter was left in place to mark the location to target the site to implant the permanent pacing lead. In patients with lower conduction disease involving the A-V junction or bundle branches, the most physiological pacing sites have been found to be the left ventricular septum or left ventricular apex. These are locations in proximity to the specialized Purkinje conduction network. These locations are not accessible using current transvenous lead-based pacing systems. It would be advantageous to be able to select the pacing site in order to model more normal conduction.
Still another advantage of a leadless pacemaker system would be increased compatibility with magnetic resonance imaging (MRI). Current pacemaker pulse generators are made of materials and/or contain shielding that is generally compatible with the high static and alternating magnetic fields of MRI. However, lead wires are typically constructed with coiled metallic conductors, which are subject to induced currents from the magnetic field. Such currents can cause unwanted stimulation of the heart, and potentially damage the pacemaker pulse generator. A leadless pacemaker system will obviously eliminate the problem of current induced in the lead wires, though proper materials selection and shielding will still have to be employed in the design of the implantable components.
Recently, the concept of a leadless, subcutaneous implantable defibrillator has been proposed e.g. 6,647,292 (Bardy). In this concept high energy electrical waveforms are delivered between electrodes implanted in subcutaneous chest regions creating sufficient energy density within the thoracic volume to terminate ventricular tachycardia (VT) or ventricular fibrillation (VF). This uses the same electrical field density concept for VT/VF termination as external application or as implanted defibrillator devices with electrodes on leads in the heart. In external defibrillation, energy is delivered between electrodes on the skin surface. In this subcutaneous approach electrodes are implanted beneath the skin but not in contact with the heart. In common implantable systems one of the defibrillation electrodes may consist of the metal enclosure of the implanted controller with the other electrode a coil on a lead placed in the right side (right ventricle) of the heart.
The subcutaneous implantable defibrillator system has no direct contact with cardiac tissue so there are added difficulties incorporating pacing therapy compared to lead-based pacemakers. To pace with subcutaneous electrodes, a sufficient electrical field must be created between two electrodes across the chest volume in order to reach pacing stimulation thresholds in the heart. This method also has no capability to precisely localize the electrical effect in the heart. Since this is a field effect, all muscles and nerves in the chest are exposed to the electrical field. The pacing pulse energy levels required to stimulate cardiac tissue using this electrical field approach are sufficiently high that chest muscle contractions and pain sensations would be associated with subcutaneous pacing. While pain occurs with high energy defibrillating discharges of all implantable defibrillators, no pain occurs with low-energy pacing using intracardiac leads. A subcutaneously implanted device implementing pacing would cause patient pain and would not be accepted when compared to a pain-free alternative. It would be highly advantageous to have a leadless system that would be capable of high energy defibrillation and also contain painless pacing capability.
In addition to using high energy electrical waveforms for the termination of VT/VF, lead-based implantable defibrillator systems typically also contain pacing algorithms that are effective in terminating VT/VF, referred to as antitachycardia pacing (ATP). For ATP, both the lead-based implantable system and the leadless subcutaneous system concepts have limitations in selecting the location of the pacing application, particularly in the left side of the heart. VT can be readily terminated using low voltage pacing stimulation if the site of the pacing is near the ventricular tachycardia focus or reentrant circuit. However, this is usually in the left ventricle, and close to the endocardium. As noted above, current pacemaker/defibrillator devices incorporate antitachycardia pacing but the pacing site is limited to the right ventricular lead or is subject to the same limitations previously described for left-sided lead placements. Further, right-sided locations have been shown to be less effective in electrophysiology laboratory testing, especially for VT's of high rate which are more serious. Pacing stimuli must stimulate cardiac tissue in the excitable region (excitable gap) of the VT reentry circuit in order to terminate the VT. Most VT circuits are located in the subendocardial layer of the left ventricle. For more rapid rate VT's, the excitable gap is small and the pacing stimuli must be very close to the VT reentry circuit for successful VT termination. In current pacemaker/defibrillator devices, if antitachycardia pacing is ineffective in terminating VT, painful high energy electrical field shocks are delivered. Therefore, it would be advantageous to be able to select the pacing site, particularly near the endocardium and in the left ventricle. Having the capability to select the location for a left ventricular lead for terminating episodes of ventricular tachycardia using antitachycardia pacing techniques would be expected to be more effective compared to current devices.
Another limitation of both the requirement of having leads and of having limited access to the left heart is in the emerging area of multisite pacing for termination of atrial and ventricular fibrillation. These arrhythmias typically arise in and are maintained by the left atrium and left ventricle. Studies have demonstrated the presence of excitable gaps within the tissue during atrial fibrillation (animal and human studies) and ventricular fibrillation (animal studies). By placing and stimulating at multiple pacing sites, regional pacing capture can be obtained during these arrhythmias. This means that if stimulation is delivered at the appropriate timing to a sufficient number of sites, in the appropriate locations, termination of atrial and ventricular fibrillation is possible. The advantage of terminating fibrillation with selected site left ventricular pacing would be the avoidance of painful high energy shocks. In this application the capability for left-sided stimulation and multi-sites of stimulation would be advantageous.
In addition to the termination of tachyarrhythmias, implanted pacemakers and defibrillators have been used to prevent tachyarrhythmias. In patients receiving permanent pacemakers, the dual chamber (DDD) mode has been shown to result in fewer episodes of AF compared to single chamber (VVI) mode in several large clinical trials. DDD pacing that incorporates simultaneous multisite stimulation of both the high right atrium and CS ostium has also been compared to standard single atrial site DDD pacing for the suppression of AF, showing a modest reduction of AF episodes. Atrial stimulation at a site or multiple sites other than the usual right atrial appendage may be advantageous for the prevention of atrial fibrillation by shortening total atrial activation time. Right atrial sites in Koch's triangle and Bachman's bundle may reduce atrial activation time by stimulating near or within atrial conduction tracts or within other tracts that are part of the normal conduction pathway. In an experimental canine model (Becker), either 4 pacing sites (2 in RA and 2 in LA) or one in the interatrial septum were required for suppression of AF. While these results are very promising, they present a technical obstacle for current pacemaker systems. The use of multisite pacing incorporating pacing sites in the left atrium for the suppression of AF has not been evaluated in humans because of all the issues of using multiple leads and in using leads within the left heart.
It follows that if AF may be able to be suppressed with multisite atrial pacing (especially in the left atrium), that VF may be able to be suppressed with multisite ventricular pacing (especially in the left ventricle). However, the difficulties associated with the implantation of multiple leads in the left ventricle has rendered this form of prevention impossible.
For these reasons, it would be desirable to accomplish stimulation without the need for lead wires. In this application we describe methods and apparatus, using acoustic energy for an implantable leadless stimulator system, that overcome limitations in pacing site selection. In co-pending applications we further describe improved stimulating devices. Methods and systems to evaluate and optimize positioning for implantation of this invention are described herein.
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